Antibodies to nucleic acids occur in systemic lupus erythematosus, in New Zealand Black/White hybrid mice with a spontaneous autoimmune disease, and in a rare lymphoma of CAF1 mice. They may react with single or double-stranded DNA or RNA, or with DNA:RNA hybrid molecules. They may belong to the 19S IgM or 7S IgG immunoglobulin class. Studies with NZB/NZW mice show a transition from 19S to 7S antibodies to nucleic acids as the mice age. Formation of such antibodies may reflect alterations in the balance between helper and suppressor T cell activities. This possibility will be explored using an in vitro antibody response system. Studies with monoclonal anti-DNA myeloma protein will explore the possibility of specific immunosuppression based on recognition of idiotype surface membrane receptors.